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GHRP-2 growth hormone releasing-hormone





GHRP-2 is a synthetic ghrelin analogue. Like ghrelin, it stimulates release of endogenous growth hormone from somatotropes in the anterior pituitary; also like ghrelin, it is synergistic with endogenous growth hormone releasing-hormone (GHRH) as well as with synthetic GHRH analogues such as Sermorelin or GRF(1-29). [3] Whereas GHRP-2 and other ghrelin analogues increase the number of somatotropes involved in the GH pulse by inhibiting somatostatin, GHRH increases the pulse amplitude per pituitary cell or somatotrope by other means.[1] Unlike ghrelin, GHRP-2 is not lipogenic meaning it does not induce fat storage. While ghrelin has a very important role in hunger, GHRP-2 as an analog of ghrelin does not increase appetite significantly.[1]

GHRP-2 is synergistic with GHRH due to secondary actions on hypothalamic neurons. [2] The quantity of GH released by a living mammal to which GHRP-2 and GHRH are administered exceeds the combined release of each compound when measured when taken alone. [2]

The neuronal excitation in the hypothalamus lasts for an hour or so with GHRP-2 dosing, quickly causing a high-amplitude pulsation of GH which tapers back to baseline by the third hour after application.[4] This pulse closely resembles natural or endogenous GH release, and for many purposes is likely superior in application to the synthetic GH circulation period of eight hours. Cellular desensitization to the effects of GH is more likely to occur with a longer, shallower pulse.[5]

Age-related GH decline, as well as other potential issues that might be treated with GHRP-2, is not a result of inability to produce GH but rather is due to a reduction in signaling. The aged pituitary of humans can still produce the same amount of GH with the same frequency, but the signaling compounds ghrelin and endogenous GHRH are released in different patterns creating a loss in GH production relative to youthful states or healthful states.[5]

In humans, a dose of 1mcg/kg (100mg for a 100kg male) of GHRP-2 when combined with a GHRH of equal dosage creates a three-hour pulse of GH that is double the amplitude of an 8 IU synthetic (e.coli derived) growth hormone dose.[4] IV, intramuscular and subcutaneous routes lead to different onset times but roughly similar peaks and declines. Due to ease of synthesis (as opposed to the complicated process of creating GH from e. coli), safety, and lower cost, GHRP-2 as part of comprehensive therapy may soon supplant conventional exogenous GH therapy.



References:

[1] Bercu, B.B., Yang, S-W., Masuda, R. and Walker, R.F. (1992) Role of selected endogenous peptides in growth hormone releasing hexapeptide (GHRP) activity: analysis of GHRH, TRH and GnRH. Endocrinology 130, 2579–2586.
[2] Chen, C., Wu, D. and Clarke, I.J. (1996) Signal transduction systems employed by synthetic GH-releasing peptides in somatotrophs. J. Endocrinol. 148, 381–386
[3] Frohman, L.A., Downs, T.R. and Chomczynski, P. (1992) Regulation of growth hormone secretion. Front. Neuroendocrinol. 13, 344–40

[4] Bowers CY, Momany F, Reynolds GA. In vitro and in vivo activity of a small synthetic peptide with potent GH releasing activity. 64th Annual Meeting of the Endocrine Society, San Francisco, 1982, p. 205
[5]Bowers CY, Momany F, Reynolds GA, Sartor O. Multiple receptors mediate GH release. 7th International Congress of Endocrinology, Quebec, Canada, 1984, p. 464.


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